Bone marrow toxicity associated with 5-fluorocytosine therapy

Area of Science:

• Pharmacology
• Toxicology
• Infectious Diseases

Background:

• Serious fungal infections necessitate aggressive treatment.
• 5-fluorocytosine (5-FC) is an antifungal agent used for severe infections.
• Bone marrow toxicity is a potential adverse effect of 5-FC therapy.

Purpose of the Study:

• To investigate the incidence and characteristics of bone marrow toxicity associated with 5-fluorocytosine (5-FC) treatment.
• To identify factors contributing to the development of 5-FC-induced bone marrow toxicity.
• To establish guidelines for safe 5-FC administration.

Main Methods:

• Retrospective analysis of 15 patients treated with 5-FC for serious fungal infections.
• Monitoring of serum 5-FC concentrations and renal function.
• Assessment of bone marrow toxicity, including leukopenia and aplasia.

Main Results:

• Bone marrow toxicity observed in 4 of 15 patients (26.7%).
• Toxicity correlated with serum 5-FC levels ≥ 125 µg/ml.
• Diminished renal function contributed to 5-FC accumulation and toxicity in three patients.
• One patient with acute renal failure and high 5-FC levels developed fatal marrow aplasia.
• Leukopenia was reversible upon dose reduction and lowering serum 5-FC levels.

Conclusions:

• Bone marrow toxicity is a significant risk with 5-FC therapy, particularly at high serum concentrations.
• Renal function plays a critical role in 5-FC clearance and toxicity.
• Close monitoring of serum 5-FC levels and renal function is essential to prevent dose-related bone marrow toxicity.
• Adjusting 5-FC dosage based on serum levels and renal status can mitigate adverse effects.